It happened around 3 a.m. Saturday when police say one of the vehicles crossed the center line on the 4100 of Wissahickon Avenue.
One of the two drivers was trapped and firefighters had to cut the roof off to free that person.
A man and woman, both in their 20s, were taken to Einstein Medical Center with multiple injuries.
Police have not said which driver was the one who crossed over and was at fault. They are continuing to investigate.